Hydrogels are used for the medical treatment of wounds, being used in the form of appropriate wound contact materials particularly wherever keeping a wound moist leads to improved wound healing (moist wound treatment). Hydrogels are typically formed using synthetic polymers based on poly(meth)acrylates, polyvinylpyrrolidone or polyvinyl alcohol. In general, such hydrogels are notable for good compatibility with living tissue.
Also known are hydrogels of polyurethanes obtainable by reaction of hydrophilic, isocyanate-functional prepolymers and a large excess of water, as described for example in EP-A 426 422, EP-A 455324, WO 9817215, WO 9913923 and WO2002060501. The large excess of water is necessary to avoid foaming due to the carbon dioxide released by the reaction of isocyanate groups with water. This means, conversely, that polyurethane hydrogels having a low level of initially added water (bubble free) are not obtainable. Thus produced polyurethane hydrogels can therefore only give off water to a (dry) wound, whereas wound fluid can only be taken up to a very limited extent.
Moreover, prior art production of polyurethane hydrogels is a slow operation which frequently has to utilize three components and in which the resulting gel still contains large amounts of unbound polyol. The synthesis usually utilizes aliphatic, isocyanate-functional prepolymers based on a polyethylene glycol, polypropylene glycol or glycerol as polyol, partly in the presence of an accelerant, for example oligoalkylene oxides having primary amino end groups; that is, three components are necessary for faster-reacting systems. The polyol is utilized in distinctly superstoichiometric amounts. It follows that the hydrogels described still contain excess polyol and activator. Furthermore, reaction times are very slow, gel point often only being reached after 90 minutes. To what extent such gels can be additized with antimicrobially active substances has not been described to date.
There are also hydrogels that are formed by free-radical crosslinking. GB-A 2086927 describes semi-IPN hydrogels which, initiated by peroxides, are formed at elevated temperature by crosslinking of low molecular weight polyacrylates in the presence of an ethanolic solution of a linear polyurethane. Subsequently, the assistant solvent ethanol is removed.
GB-A 2131442 describes low molecular weight polyallyl compounds and GB 2150938 describes hydroxyethyl methacrylate (HEMA) and other monoacrylates as external, free-radically polymerizing monomers. These prior art references likewise involve an assistant solvent, such as ethanol, and peroxides at elevated temperature.
EP-A 351 364 describes hydrogels from N,N-dimethylacrylamide, fluorous polymers and crosslinkers, possible crosslinkers including polyols, such as polyvinyl alcohol or triethylene glycol, reacted with unsaturated isocyanates, such as MOI (methacryloyloxyethyl isocyanate) or TMI (α,α-dimethyl-3-isopropenylbenzyl isocyanate). Crosslinking was effected by initiation with UV or free-radical initiators. The same disadvantages as described above apply. Moreover, UV crosslinking in body contact is critical (reaction with the skin, eye protection for patient and for medical personnel).
US 2005 0271727 describes hydrogels formed by redox polymerization from polyvinyl alcohol and a crosslinker prepared, at some cost and inconvenience, from HEMA and glycolide according to Furch et al, Polymer, (1998) 39 (10), 1977-1982.
There is therefore a need for a polyurethane hydrogel which when needed can be formed using just small amounts of water and therefore is capable, when in contact with a wound, of additionally taking up wound fluid. Of course, the polyurethane hydrogel shall continue to be able to give off water to (dry) wounds. Since the polyurethane hydrogel is if necessary only formed in a wound or other body opening (in the case of endoscopic interventions for example), crosslinking has to take place without significant exotherm. The use of radiative curing (UV crosslinking for example) is to be avoided because of the high cost and inconvenience. All liquid precursors as well as the polyurethane hydrogel itself shall possess good biocompatibility; and the use of organic solvents shall be avoided.